Amgen's KRAS drug continues to deliver but faces 'curse' of high expectations

In June, Amgen’s KRAS inhibitor became the first drug of its class to post clinical data, stopping tumor growth or shrinking tumors in 90% of lung cancer patients. Now, the company is unveiling data for the highest dose of the drug, showing it kept cancer at bay in 100% of lung cancer patients and shrank tumors in more than half of them. 

The first data for the drug, AMG 510, included 10 patients with non-small cell lung cancer (NSCLC) who had been on treatment long enough to be evaluated. Presented at the annual meeting of the American Society for Clinical Oncology (ASCO), they included patients on four different doses of the drug: 180 mg, 360 mg, 720 mg and maxing out at 960 mg. The new data, presented Sunday at the World Conference on Lung Cancer, includes 23 evaluable NSCLC patients with 13 taking the target dose, 960 mg. 

Seven of the 13 (54%) saw their tumors shrink, while the remaining six (46%) had their tumors stop growing, showing the drug could control the disease in 100% of patients. 

Looking at all 34 NSCLC patients enrolled, there were no side effects that limited treatment or that led patients to quit the study. The worst side effects reported were anemia and diarrhea. 

RELATED: Amgen's KRAS drug shows promise in 2 additional cancers: colorectal and appendiceal

"These new data reinforce the earlier positive response rate we shared at ASCO in more non-small cell lung cancer patients receiving AMG 510," said David Reese, M.D., Amgen’s R&D chief, in a statement. "We remain enthusiastic about the promise of AMG 510 and continue to rapidly advance its development program both as monotherapy and in combination." 

In this study, Amgen is testing AMG 510 as a single agent to be used after the patient has exhausted other treatments. In other words, the drug is putting up encouraging numbers in a difficult-to-treat group of cancer patients. And unlike patients with other mutations, such as HER2 or BRAF, patients with KRAS-mutated cancers still don’t have a treatment tailored to their mutation, largely due to the lack of obvious binding sites on the KRAS protein. 

That said, JPMorgan analysts noted that the new data set “might illustrate the curse of sky high expectations.” Amgen stock was down 4% in premarket trading. 

“The data, in totality, are still quite impressive … but initial investor reaction on the heels of the original 3-for-3 showing at ASCO is one of relative disappointment,” the analysts wrote. At ASCO, the data included a 100% response rate in three NSCLC patients who had received the highest dose of AMG 510.

RELATED: ASCO: Amgen's closely watched KRAS drug, first to clinic, shrinks NSCLC, curbs colorectal tumors

Jefferies analysts called the data “very solid,” but considered the investor response “as a potential short-term trading dynamic, where the Street is a little disappointed but docs will like the data for an unmet need (and large market) and the drug will move toward FDA approval over the next 1-2 years.” 

Its safety data “could be positive for combination therapy,” the Jefferies analysts said, noting that Amgen is already enrolling a phase 1b combination study. 

In addition to combining AMG 510 with checkpoint inhibitors, Amgen also wants to move it into earlier lines of treatment. And it’s showing promise in more than just lung cancer. The ASCO data showed that the drug stopped the growth of colorectal tumors—but did not shrink them. At the time, Sanket Agrawal, general manager of the KRAS program at Amgen, pointed out that those results came from patients who were being treated with the two lowest doses of AMG 510, hinting higher doses might do even better. 

In July, the Big Biotech revealed in its second-quarter earnings call that the drug shrank tumors in patients with colorectal cancer and cancer of the appendix. A company spokesperson confirmed the responses were seen in patients on the higher doses. 

Now, all eyes are on the European Society for Medical Oncology meeting at the end of the month, where analysts expect to see data from yet more patients and other tumor types.